PARP1-MGMT complex underpins pathway crosstalk in O-methylguanine repair.

DNA lesions induced by alkylating agents are repaired by two canonical mechanisms, base excision repair dependent on poly(ADP) ribose polymerase 1 (PARP1) and the other mediated by O-methylguanine (OmeG)-DNA methyltransferase (MGMT) in a single-step catalysis of alkyl-group removal. OmeG is the most cytotoxic and mutagenic lesion among the methyl adducts induced by alkylating agents. Although it can accomplish the dealkylation reaction all by itself as a single protein without associating with other repair proteins, evidence is accumulating that MGMT can form complexes with repair proteins and is highly regulated by a variety of post-translational modifications, such as phosphorylation, ubiquitination, and others.

Temporal regulation of agonist efficacy at 5-hydroxytryptamine (5-HT)1A and 5-HT 1B receptors.

Coactivation of purinergic (P 2Y) receptors reduces agonist efficacy at serotonin 1B (5-HT 1B), but not 5-HT 1A receptors. Herein, we report that pretreatment for 5 min with the P 2Y receptor agonist ATP reduced agonist responsiveness at the 5-HT 1A, but not at the 5-HT 1B, receptor. The effect of ATP pretreatment on the 5-HT 1A receptor response rapidly reversed within a 10 min time frame between P 2Y receptor and 5-HT 1A receptor activation.